Angiotensin receptor neprilysin inhibitor LCZ696: pharmacology, pharmacokinetics and clinical development.

Heart failure still has a significant disease burden with poor outcomes worldwide despite advances in therapy. The standard therapies have been focused on blockade of renin-angiotensin-aldosterone system with angiotensin-converting enzyme inhibitors, angiotensin receptor blockers and mineralocorticoid antagonists and the sympathetic nervous system with β-blockers. The natriuretic peptide system is a potential counter-regulatory system that promotes vasodilatation and natriuresis. Angiotensin receptor neprilysin inhibitors are a new class drug capable of blocking the renin-angiotensin-aldosterone system and enhancing the natriuretic peptide system to improve neurohormonal balance. The success of the PARADIGM-HF trial with LCZ696 and its approval for heart failure treatment is likely to generate a paradigm shift. This review summarises the current knowledge of LCZ696 with a focus on pharmacology, pharmacokinetics and pharmacodynamics, mechanisms of action, clinical efficacy and safety.

尽管治疗方法有所进步，但心力衰竭在全球范围内仍然是一种疾病负担沉重且预后不良的疾病。标准治疗一直侧重于使用血管紧张素转换酶抑制剂、血管紧张素受体阻滞剂和盐皮质激素拮抗剂阻断肾素 - 血管紧张素 - 醛固酮系统，以及使用β受体阻滞剂阻断交感神经系统。利钠肽系统是一种潜在的反调节系统，可促进血管舒张和利钠排尿。血管紧张素受体脑啡肽酶抑制剂是一类新型药物，能够阻断肾素 - 血管紧张素 - 醛固酮系统并增强利钠肽系统，以改善神经激素平衡。PARADIGM - HF试验中LCZ696的成功以及其被批准用于心力衰竭治疗很可能会引发范式转变。这篇综述总结了目前关于LCZ696的知识，重点关注其药理学、药代动力学和药效学、作用机制、临床疗效和安全性。